Objectives To examine the effect of nystatin oral rinse on oral Candida species and Streptococcus mutans carriage. Materials and Methods Twenty healthy adults with oral candidiasis participated in the single-arm clinical trial and received Nystatin oral rinse for 7 days, 4 applications/day, 600,000 International Units/application. Demographic-socioeconomic-oral-medical conditions were obtained. Salivary and plaque Candida species and Streptococcus mutans were assessed at baseline, 1-week and 3-month follow-ups. Twenty-four salivary cytokines were assessed. Candida albicans isolates underwent Nystatin susceptibility test. Results Half of participants (10/20) were free of salivary C. albicans after using Nystatin rinse. Salivary S. mutans was significantly reduced at 3-month follow-up (p 0.05). No C. albicans isolates were resistant to Nystatin. Furthermore, salivary cytokines Eotaxin and Fractalkine were significantly reduced at 3 months follow-up among participants responded to Nystatin rinse (p S. mutans salivary carriage. Future clinical trials are warranted to comprehensively assess the impact of antifungal treatment on the oral flora other than S. mutans and Candida. Clinical Relevance : Due to the potential cariogenic role of oral Candida species, antifungal approaches shed new light on the prevention and management of dental caries from a fungal perspective.